SEARCH · PubMed Health

Results for “Functional perturbation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

PubMed1993

A bacterial protease perturbs the paracellular barrier function of transporting epithelial monolayers in culture.

Tight junctions between cells and adhesion to the substratum maintain the barrier function of epithelia throughout the body. Damage to the epithelial barrier by microbial products allows penetration of bacteria and promotion of infection. We studied the effects of Pseudomonas elastase (PE) on the barrier function of epithelia by using Madin-Darby canine kidney (MDCK) epithelial cells; these cells form tight junctions (zonula occludens [ZO]) in vitro. PE decreased electrical resistance across the monolayers in a concentration- and time-dependent manner. Immunostaining of selected proteins of the ZO and zonula adherens was used to explore the effects of PE on junctional proteins. PE-treated monolayers of MDCK cells had markedly decreased immunostaining of ZO-1, a protein of the ZO, but light microscopy of PE-treated cells revealed no obvious morphologic changes. A chromium release assay indicated that, even with marked changes in transmonolayer electrical resistance, the permeability defect was not due to membrane disruption. Fluorescence staining of F-actin indicated diminution of cellular microfilaments in PE-treated cells, but E cadherin (uvomorulin), a protein of the zonula adherens, was unaffected by the enzyme. Elastases from porcine pancreas and human leukocytes with similar enzymatic activity (6 U/ml) did not decrease transmonolayer electrical resistance or degrade ZO-1. These results suggest that PE disturbs the barrier function of epithelial monolayers, in part, by changing the cell architecture and altering at least one protein of the ZO.

Animals↗

PubMed2006

Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice.

Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo(-/-) mice. Surprisingly, myo(-/-) mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo(-/-) mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent.

Actins↗

PubMed1983

Perturbation of upper gastrointestinal function by cold stress.

To study the effects of stressful stimulus (cold pain) upon postprandial gastric, duodenal, and pancreatic function, nine healthy adult volunteers were intubated and then given two identical liquid meals, (199 cal (789 KJ) 240 ml), each being ingested during a period of irregular fasting gastroduodenal motility. Ten minutes after each meal the subjects received, in randomised order, either a test or control stimulus. The test stimulus consisted of repeated one minute immersions of a hand into ice water, with 15 seconds recovery between immersions, for a total of 20 minutes, while for the control, water at 37 degrees C was used. Serial samples of gastric and duodenal contents allowed estimation of changes in gastric emptying and acid secretion, together with pancreatic trypsin output, by a double marker perfusion technique. Measurements of blood pressure, pulse, and finger temperature acted as extra-intestinal indices of autonomic response to the stimuli. Cold pain significantly delayed gastric emptying and produced a biphasic alteration in both gastric secretion and pancreatic trypsin output, with an initial reduction during the response to the stress followed by an increase during the post-stress period. Our findings show that the normal postprandial function of the upper gut can be measurably disturbed by a stressful stimulus. The coincidence of these disturbances with other extra-intestinal autonomic changes suggests that they are a further manifestation of the somatic response to a stress.

Adult↗

PubMed1989

Studies on the mechanisms causing inhibition of insulin secretion in rat pancreatic islets exposed to human interleukin-1 beta indicate a perturbation in the mitochondrial function.

This study aimed at a more detailed characterization of the mechanisms by which interleukin 1 (IL-1) inhibits insulin secretion. For this purpose, isolated rat pancreatic islets were kept in tissue culture for 5 days in medium RPMI 1640 plus 10% calf serum. The islets were subsequently transferred to the same culture medium containing various test substances plus 1% human serum with or without 25 U/ml human recombinant IL-1 beta. After a culture period of 48 h the islet structure was examined in the electron microscope and the islet function studied in short term incubations in the absence of IL-1. Islets exposed to IL-1 showed ultrastructural signs of degeneration in 10-20% of the B cells while such changes were not found in other types of islet cells. An increased number of secondary lysosomes and occasional myelin figures were observed in the B cells exposed to IL-1. These ultrastructural alterations were, however, reversed in islets cultured in cytokine-free medium for 6 days after the IL-1 treatment. In islets cultured in the presence of 11.1 mM glucose only, or 11.1 mM glucose plus 10 mM nicotinamide, 61 mM dimethyl area, 2 micrograms/ml indomethacin, 10 microM 4-bromophenacyl bromide or 10 microM nordihydroguaiaretic acid, 10 microM phenantroline, and 0.1 or 1.0 microgram/ml cyclosporin A, IL-1 reduced the insulin release by 64-85%. Culture at 5.6 mM glucose did not modify the IL-1-induced inhibition of insulin release, whereas a significant protective effect was observed at 28 or 56 mM glucose. The DNA content in IL-1-exposed islets cultured at 11.1 mM glucose was decreased by about 20% but not in islets cultured at other glucose concentrations. The D-[5-3H]glucose utilization at 16.7 mM glucose was unaffected by IL-1, whereas the oxidation of D-[6-14C]glucose was reduced by 50%. The present results suggest that IL-1-induced inhibition of insulin secretion is related to a disturbed mitochondrial function. This effect is not counteracted by a poly(ADP-ribose) synthetase inhibitor, a hydroxyl radical scavenger, an iron chelator, a T lymphocyte-specific immunosuppressive drug, or inhibitors of phospholipase A2 or inhibitors of prostaglandin and leukotriene synthesis. Thus, IL-1-induced inhibition of insulin secretion seems not to be mediated by the same mechanisms as those causing alloxan- or streptozotocin-induced damage of B cells. Furthermore, the action of IL-1 does not appear to be mediated via arachidonic acid metabolism. Glucose affords some protection, probably by enhancing the B cell mitochondrial function.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetophenones↗

PubMed2026

Perturbing H-NS function reveals roles in restricting virulence heterogeneity and pathogen adaptation.

Xenogeneic silencers, such as histone-like nucleoid structuring protein (H-NS), are critical for maintaining horizontally acquired genes in bacterial genomes and minimizing fitness costs associated with inappropriate expression. For bacterial pathogens, this has enabled the acquisition of costly virulence regulons, with H-NS balancing the need for tight silencing with rapid expression in host environments. For Salmonella enterica serovar Typhimurium (STm), survival in these environments relies on phenotypic heterogeneity in virulence gene expression and evolutionary adaptation. Although complete loss of hns is highly deleterious in STm, how subtle impairments to this global silencer disrupt heterogeneity in virulence gene expression and alter adaptation to host environments remains poorly understood. Here, we identify an STm hns hypomorph strain and find that its reduced H-NS DNA-binding affinity increases the proportion of virulence-expressing cells, resulting in enhanced epithelial cell infection in vitro. Furthermore, through experimental evolution in intracellular-like conditions in vitro, we demonstrate that both wild-type and mutant populations converge on disrupting the SPI-2 virulence regulon to improve fitness; however, the mutant population also acquires distinct adaptive mutations to resolve the underlying dysregulation in gene expression. These results suggest that H-NS sets single-cell virulence activation thresholds and that even minor disruptions to its silencing function impact pathogen adaptation, highlighting its role as a critical evolutionary buffer.

Salmonella typhimurium↗

PubMed1994

Substitution at Pro385 of GLUT1 perturbs the glucose transport function by reducing conformational flexibility.

The mammalian glucose transporter, GLUT1, is capable of alternating between two conformations which expose either an outward- or inward-facing ligand binding site. The possibility that these conformational changes are related to the presence of prolines and glycines in transmembrane region 10 was investigated by site-directed mutagenesis. Chinese hamster ovary clones which were transfected with Pro385-->Ile and Pro385-->glycine mutations of GLUT1 were shown, by Western blotting and cell surface carbohydrate labelling, to have expression levels which were comparable with the wild type. The transport activity was markedly reduced as a result of the Pro385-->isoleucine but not in the Pro385-->glycine mutation. The loss of transport activity in the Pro385-->isoleucine clone was associated with loss of labeling by the exofacial photoaffinity ligand, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2- propylamine (ATB-BMPA), but there was no loss in labeling by the inside site-directed ligand cytochalasin B. These results suggest that the transporter cannot adopt the outward-directed conformation in the Pro385-->isoleucine clone. By contrast, the glycine substitution for proline at this position resulted in a retention of the ligand binding properties at both inside and outside sites. We suggest a putative mode of operation of the transporter which involves conformational flexibility about the prolines in transmembrane segment 10 such that helices 11 and 12 can alternately either pack against the outside (ATB-BMPA binding) site in helices 7, 8, and 9 or against the inner (cytochalasin B binding) site at the base of transmembrane segment 10.

Amino Acid Sequence↗

PubMed2004

Perturbative calculation of one-point functions of one-dimensional single-species reaction-diffusion systems.

Perturbations around autonomous one-dimensional single-species reaction-diffusion systems are investigated. It is shown that the parameter space corresponding to the autonomous systems is divided into two parts: In one part, the system is stable against the perturbations, in the sense that the largest relaxation time of the one-point functions changes continuously with perturbations. In the other part, however, the system is unstable against perturbations, so that any small perturbation drastically modifies the large-time behavior of the one-point functions.

Journal Article↗

PubMed1982

Propranolol effects on autonomic function in hypertensive men.

Beta blocker antihypertensive effects are incompletely understood, and may involve alterations in the autonomic nervous system. We studied autonomic function in 12 essential hypertensive men during treatment with placebo and chronic oral propranolol. Propranolol reduced blood pressure and heart rate (both p less than 0.01) with an associated increase in baroreflex sensitivity during phenylephrine testing (p less than 0.02), though amyl nitrite-tested baroreflex sensitivity was unchanged; blood pressure decrement did not correlate with baroreflex enhancement. Response to the cold pressor test and the blood pressure decrement to phentolamine alpha blockade were unaltered by propranolol, suggesting unchanged efferent sympathetic function; nor were several biochemical indices of sympathetic nervous activity influenced by propranolol. Propranolol does perturb autonomic function in man, but the perturbations do not correlate with blood pressure decrement; nor are physiologic or biochemical indices of efferent sympathetic activity reduced by propranolol.

Adult↗

PubMed2006

A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules.

Rapid and reversible methods for perturbing the function of specific proteins are desirable tools for probing complex biological systems. We have developed a general technique to regulate the stability of specific proteins in mammalian cells using cell-permeable, synthetic molecules. We engineered mutants of the human FKBP12 protein that are rapidly and constitutively degraded when expressed in mammalian cells, and this instability is conferred to other proteins fused to these destabilizing domains. Addition of a synthetic ligand that binds to the destabilizing domains shields them from degradation, allowing fused proteins to perform their cellular functions. Genetic fusion of the destabilizing domain to a gene of interest ensures specificity, and the attendant small-molecule control confers speed, reversibility, and dose-dependence to this method. This general strategy for regulating protein stability should enable conditional perturbation of specific proteins with unprecedented control in a variety of experimental settings.

Animals↗

PubMed2000

Haemostatic function in patients undergoing coronary artery bypass grafting: peroperative perturbations and relations to saphenous vein graft closure.

Vein graft failure remains a major problem after coronary artery bypass grafting. Occlusion in the first weeks usually is caused by thrombosis, whereas intimal hyperplasia and eventually atherosclerotic changes with superimposed thrombus formation underlie subsequent closure. The present investigation was conducted as a pilot study to examine whether perturbations of haemostatic function predispose to early saphenous vein graft occlusion after coronary artery bypass grafting. Pre- and postoperative determinations (performed on the first, third, and sixth postoperative days) of haemostatic factors and inhibitors were related to the presence of graft occlusion assessed by angiography at 3 months after surgery in 100 men undergoing elective coronary artery bypass grafting for stable angina pectoris. Occlusion of one or more vein grafts within three months of surgery occurred in 23 of the 100 patients examined. The percentage increase in plasma plasminogen activator inhibitor-1 activity on the first postoperative day was significantly higher in patients who subsequently were found to have vein graft occlusion (p<0.05). Otherwise no postoperative haemostatic measurements were found to predict early vein graft closure. A perturbed plasma plasminogen activator inhibitor-1 response to coronary artery bypass grafting tentatively could be added to the vessel-specific factors that remain the main determinants of early vein graft closure.

Adult↗

PubMed2003

Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice.

Among the five different muscarinic receptors that have been cloned and characterized, M2 and M4 receptors are localized both post- and presynaptically and are believed to have a pronounced autoreceptor role. The functional importance of these receptors in the regulation of acetylcholine release in the hippocampus and in cognitive processes was investigated by using M2 and M4 receptor single knockout (KO) as well as M2/M4 receptor double KO mice. We found profound alterations in acetylcholine homeostasis in the hippocampus of both M2- and M4-KO mice as well as of the combined M2/M4-KOs, as assessed by in vivo microdialysis. Basal acetylcholine efflux in the hippocampus was significantly increased in M4-KO and was elevated further in M2/M4-KOs. The increase in hippocampal acetylcholine induced by local administration of scopolamine was markedly reduced in M2-KO and completely abolished in M2/M4-KOs. In M2-KO and much more in M2/M4-KOs, the increase in hippocampal acetylcholine triggered by exposure to a novel environment was more pronounced both in amplitude and duration, with a similar trend observed for M4-KOs. Dysregulation of cholinergic function in the hippocampus, as it could result from perturbed autoreceptor function, may be associated with cognitive deficits. Importantly, M2- and M2/M4-KO, but not M4-KO, animals showed an impaired performance in the passive avoidance test. Together these results suggest a crucial role for muscarinic M2 and M4 receptors in the tonic and phasic regulation of acetylcholine efflux in the hippocampus as well as in cognitive processes.

Acetylcholine↗

PubMed1977

Oxidative phosphorylation. Halide-dependent and halide-independent effects of triorganotin and trioganolead compounds on mitochondrial functions.

1. Each of five triorganotin and five triorganolead compounds was shown to perturb mithochondrial functions in three different ways. One is dependent and two are independent of Cl- in the medium. 2. Structure-activity relationships for the three interactions are described, and compounds suitable as tools for the separate study of each process are defined. 3. In a Cl- -containing medium trimethyltin, triethyltin, trimethyl-lead, triethyl-lead and tri-n-propyl-lead all produce the same maximum rate of ATP hydrolysis and O2 uptake; this rate is much less than that produced by uncoupling agents such as 2,4-dinitrophenol. 4. Increase in ATP hydrolysis and O2 uptake are measures on energy ultilization when triogranotin and triorganolead compounds bring about an exchange of external C1- for intramitochondrial OH- ions. Possible rate-limiting steps in this process are discussed. 5. In a C1- -containing medium ATP synthesis linked to the oxidation of beta-hydroxybutyrate or reduced cytochrone c is less inhibited by triethyltin or triethyl-lead than is ATP synthesis linked to the oxidation of succinate, pyruvate or L-glutamate. 6. The inhibition of ATP synthesis linked to the oxidation of both beta-hydroxybutyrate and reduced cytochrome c consists of two processes: one is a limited uncoupling and is C1- -dependent and the other is a C1- -independent inhibition of the energy-conservation system. 7. The different sensitivities to inhibition by triethyltin of mitochondrial functions involving the oxidation of beta-hydroxybutyrate and succinate are compared and discussed.

Adenosine Triphosphate↗

PubMed2000

Analytical density functional theory of homogeneous vapor condensation

Starting from an exact gradient transcription of the perturbative density functional theory of homogeneous vapor condensation, we propose an analytical approximation that reproduces the density profile and free energy of critical fluctuations to high accuracy. For a broad variety of substances, including nonpolar, weakly polar, and metallic liquids, the method predicts nucleation rates that are orders of magnitude closer to experiment than those from the classical approach. The present treatment incorporates detailed molecular theory into macroscopic modeling.

Journal Article↗

PubMed2001

Metallothionein overexpression in human trophoblastic cells protects against cadmium-induced apoptosis.

Proper functioning of trophoblastic cells is essential for maintenance of the placenta and development of the embryo/fetus. Exposure of trophoblasts to toxic exogenous factors, such as cadmium (Cd), perturbs placental function and affects fetal outcome. Cellular responses to Cd exposure include induction of the metal-binding protein, metallothionein (MT), and initiation of apoptosis. To analyze the functional relationship between cellular MT levels and apoptosis in trophoblasts, we have examined the effects of DNA transfection-mediated alterations in MT levels on trophoblastic function and apoptosis, with and without Cd exposure, using the trophoblast-like JEG-3 human choriocarcinoma cell line. JEG-3 cells stably transfected with human MT-IIa cDNA expression constructs, in either sense or antisense orientation, were unchanged in human chorionic gonadotropin (hCG) production or expression of the apoptotic markers, bcl-2 and CPP-32. However, MT overexpression significantly prolonged the recovery time of intracellular Ca flux, whereas reduced basal MT increased the incidence of apoptosis as determined by morphology and terminal deoxynucleotidyl end labeling (TUNEL) staining. Upon Cd exposure, a dose-dependent decrease in hCG secretion was seen in all JEG-3 cultures, without any correlation to basal MT expression. Basal MT levels, however, significantly affected the extent of apoptosis, the incidence being inversely related to basal MT level. These results suggest that while MT does not ameliorate heavy-metal induced perturbation of some trophoblastic functions, its expression is critical for protection of these cells from Cd-induced apoptosis and could act to maintain placental integrity in cases of maternal Cd exposure.

Apoptosis↗

PubMed2006

Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma modulate epithelial barrier function in Madin-Darby canine kidney cells through mitogen activated protein kinase signaling.

BACKGROUND: The tight junction is a dynamic structure that is regulated by a number of cellular signaling processes. Occludin, claudin-1, claudin-2 and claudin-3 are integral membrane proteins found in the tight junction of MDCK cells. These proteins are restricted to this region of the membrane by a complex array of intracellular proteins which are tethered to the cytoskeleton. Alteration of these tight junction protein complexes during pathological events leads to impaired epithelial barrier function that perturbs water and electrolyte homeostasis. We examined MDCK cell barrier function in response to challenge by the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). RESULTS: Exposure of MDCK cells to TNFalpha/IFNgamma resulted in a marked sustained elevation of transepithelial electrical resistance (TER) as well as elevated paracellular permeability. We demonstrate that the combination of TNFalpha/IFNgamma at doses used in this study do not significantly induce MDCK cell apoptosis. We observed significant alterations in occludin, claudin-1 and claudin-2 protein expression, junctional localization and substantial cytoskeletal reorganization. Pharmacological inhibition of ERK1/2 and p38 signaling blocked the deleterious effects of the proinflammatory cytokines on barrier function. CONCLUSION: These data strongly suggest that downstream effectors of MAP kinase signaling pathways mediate the TNFalpha/IFNgamma-induced junctional reorganization that modulates MDCK cell barrier function.

Animals↗

PubMed2000

The role of a mitochondrial pathway in the induction of apoptosis by chemicals extracted from diesel exhaust particles.

We are interested in the cytotoxic and proinflammatory effects of particulate pollutants in the respiratory tract. We demonstrate that methanol extracts made from diesel exhaust particles (DEP) induce apoptosis and reactive oxygen species (ROS) in pulmonary alveolar macrophages and RAW 264.7 cells. The toxicity of these organic extracts mimics the cytotoxicity of the intact particles and could be suppressed by the synthetic sulfhydryl compounds, N-acetylcysteine and bucillamine. Because DEP-induced apoptosis follows cytochrome c release, we studied the effect of DEP chemicals on mitochondrially regulated death mechanisms. Crude DEP extracts induced ROS production and perturbed mitochondrial function before and at the onset of apoptosis. This mitochondrial perturbation follows an orderly sequence of events, which commence with a change in mitochondrial membrane potential, followed by cytochrome c release, development of membrane asymmetry (annexin V staining), and propidium iodide uptake. Structural damage to the mitochondrial inner membrane, evidenced by a decrease in cardiolipin mass, leads to O-*2 generation and uncoupling of oxidative phosphorylation (decreased intracellular ATP levels). N-acetylcysteine reversed these mitochondrial effects and ROS production. Overexpression of the mitochondrial apoptosis regulator, Bcl-2, delayed but did not suppress apoptosis. Taken together, these results suggest that DEP chemicals induce apoptosis in macrophages via a toxic effect on mitochondria.

Air Pollutants↗

PubMed2000

Flexible community structure correlates with stable community function in methanogenic bioreactor communities perturbed by glucose.

Methanogenic bioreactor communities were used as model ecosystems to evaluate the relationship between functional stability and community structure. Replicated methanogenic bioreactor communities with two different community structures were established. The effect of a substrate loading shock on population dynamics in each microbial community was examined by using morphological analysis, small-subunit (SSU) rRNA oligonucleotide probes, amplified ribosomal DNA (rDNA) restriction analysis (ARDRA), and partial sequencing of SSU rDNA clones. One set of replicated communities, designated the high-spirochete (HS) set, was characterized by good replicability, a high proportion of spiral and short thin rod morphotypes, a dominance of spirochete-related SSU rDNA genes, and a high percentage of Methanosarcina-related SSU rRNA. The second set of communities, designated the low-spirochete (LS) set, was characterized by incomplete replicability, higher morphotype diversity dominated by cocci, a predominance of Streptococcus-related and deeply branching Spirochaetales-related SSU rDNA genes, and a high percentage of Methanosaeta-related SSU rRNA. In the HS communities, glucose perturbation caused a dramatic shift in the relative abundance of fermentative bacteria, with temporary displacement of spirochete-related ribotypes by Eubacterium-related ribotypes, followed by a return to the preperturbation community structure. The LS communities were less perturbed, with Streptococcus-related organisms remaining prevalent after the glucose shock, although changes in the relative abundance of minor members were detected by morphotype analysis. A companion paper demonstrates that the more stable LS communities were less functionally stable than the HS communities (S. A. Hashsham, A. S. Fernandez, S. L. Dollhopf, F. B. Dazzo, R. F. Hickey, J. M. Tiedje, and C. S. Criddle, Appl. Environ. Microbiol. 66:4050-4057, 2000).

Anaerobiosis↗

PubMed2005

Orbital-dependent correlation energy in density-functional theory based on a second-order perturbation approach: success and failure.

We have developed a second-order perturbation theory (PT) energy functional within density-functional theory (DFT). Based on PT with the Kohn-Sham (KS) determinant as a reference, this new ab initio exchange-correlation functional includes an exact exchange (EXX) energy in the first order and a correlation energy including all single and double excitations from the KS reference in the second order. The explicit dependence of the exchange and correlation energy on the KS orbitals in the functional fits well into our direct minimization approach for the optimized effective potential, which is a very efficient method to perform fully self-consistent calculations for any orbital-dependent functionals. To investigate the quality of the correlation functional, we have applied the method to selected atoms and molecules. For two-electron atoms and small molecules described with small basis sets, this new method provides excellent results, improving both second-order Moller-Plesset expression and any conventional DFT results significantly. For larger systems, however, it performs poorly, converging to very low unphysical total energies. The failure of PT based energy functionals is analyzed, and its origin is traced back to near degeneracy problems due to the orbital- and eigenvalue-dependent algebraic structure of the correlation functional. The failure emerges in the self-consistent approach but not in perturbative post-EXX calculations, emphasizing the crucial importance of self-consistency in testing new orbital-dependent energy functionals.

Algorithms↗